Risk of breast cancer (BC) increases in the period immediately following pregnancy. BCs that occur in the post-partum period have more aggressive histopathological features, are more likely to metastasize, and are associated with worse patient outcomes. On average, they also affect younger women and may represent a substantial proportion of early onset breast cancer (EOBC), a phenomenon that disproportionately affects racial/ethnic minority populations, such as Hispanics and African American (AA) women. We propose that pregnancy enhances development of BC in women whose breast tissue is vulnerable to the promotional effects of pregnancy via as yet unknown genetic and/or environmental factors and that this vulnerability explains at least part of the increased risk of EOBC and poor outcomes observed in women with higher fertility. The immediate objective of this research project is to examine epigenetic profiles of BCs that occur in the transient high-risk post-partum period versus those diagnosed outside of this period. Studies will be conducted in BC case series of Hispanic women, a population characterized by high parity. Our specific aims are to: 1) Define the risk factors, tumor sub-types, and clinicopathological characteristics associated with BCs occurring in the post-partum period of increased risk relative to those outside this period in Hispanic women; 2) Test the hypothesis that methylation of specific protein-coding gene promoters is more frequent in tumors that are diagnosed in the post-partum period of increased risk vs. those occurring outside the transient high risk period; and, 3) Test the hypothesis that miRNA genes are more likely to be epigenetically altered in tumors diagnosed in the post-partum period. Results of the proposed work may further elucidate possible mechanisms that play a role in pre-menopausal EOBC, particularly those mechanisms that are temporally related to a recent pregnancy. PUBLIC HEALTH RELEVANCE: The proposed studies have tremendous relevance to elucidating breast cancer health disparities pertaining to tumors that occur in pre-menopausal women, which disproportionately affect racial/ethnic minority populations, including Hispanic and African-American women.